A Role for Prostacyclin (Pgi2) in Excessive Menstrual Bleeding

Smith, Stephen K.; Kelly, Regis B.; Abel, M. H.; Dt, Baird

doi:10.1016/s0140-6736(81)92862-2

Cited by 111 publications

(38 citation statements)

References 9 publications

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“…Synthesis of PGI 2 and nitric oxide are also high in menstrual blood collected from menorrhagic endometrium of women presenting with excessive menstrual bleeding (Smith et al, 1981b;Makarainen and Ylikorkala, 1986). This finding indicates that the degree or duration of menstrual bleeding in women diagnosed with menorrhagia may be augmented after an increase in vasodilatatory factors.…”

Section: Europe Pmc Funders Author Manuscriptsmentioning

confidence: 99%

Cyclooxygenase enzymes and prostaglandins in pathology of the endometrium

Sales¹

2003

Reproduction

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Prostaglandins are bioactive lipids produced from arachidonic acid by cyclooxygenase (COX) enzymes and specific terminal prostanoid synthase enzymes. After biosynthesis, prostaglandins exert an autocrine-paracrine function by coupling to specific prostanoid G protein-coupled receptors to activate intracellular signalling and gene transcription. For many years, prostaglandins have been recognized as key molecules in reproductive biology by regulating ovulation, endometrial physiology and proliferation of endometrial glands and menstruation. More recently, a role for COX enzymes and prostaglandins has been ascertained in reproductive tract pathology, including carcinomas, menorrhagia, dysmenorrhoea and endometriosis. Although the mechanism by which prostaglandins modulate these pathologies is still unclear, a large body of evidence supports a role for COX enzymes, prostaglandins and prostaglandin receptor signalling pathways in angiogenesis, apoptosis and proliferation, tissue invasion and metastases and immunosuppression. Here, an overview is provided of some of the findings from these studies with specific emphasis on the role of COX enzymes, prostaglandin E 2 and F 2α in disorders of endometrial proliferation and menstruation in non-pregnant women.The arachidonic acid cascade generates a family of bioactive lipids, including prostaglandins, thromboxanes and leukotrienes that modulate diverse physiological and pathophysiological responses in the reproductive tract. There has been a great deal of interest over the past few years in the involvement of arachidonic acid metabolites in pathology. However, there is still much uncertainty about the manner in which they contribute to specific phenotypic cellular changes that may precipitate pathophysiology. The focus of this review is to provide some insight into the role of cyclooxygenase (COX) enzymes, prostaglandin E 2 (PGE 2 ) and PGF 2α and their respective receptors in reproductive pathophysiology, with specific regard to disorders of endometrial proliferation and dysfunctional menstruation.The kinetics of the prostaglandin biosynthetic pathway is driven by the availability of free arachidonic acid. When released from plasma membrane phospholipids or dietary fatty acids, after activation of phospholipase A2 (PLA2) or PLC, arachidonic acid is cyclized and oxygenated by COX enzymes by addition of the 15-hydroperoxy group to form prostaglandin G 2 (PGG 2 ). The hydroperoxy group of PGG 2 is reduced to the hydroxy group of PGH 2 (Marnett, 1992) (Fig. 1). This intermediate serves as the substrate for terminal prostanoid synthase enzymes. These enzymes are named according to the prostaglandin they produce, such that prostaglandin D 2 is synthesized by prostaglandin-D-synthase (PGDS), prostaglandin E 2 (PGE 2 ) by prostaglandin-E-synthase (PGES); prostaglandin F 2α by

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Section: Europe Pmc Funders Author Manuscriptsmentioning

confidence: 99%

Cyclooxygenase enzymes and prostaglandins in pathology of the endometrium

Sales¹

2003

Reproduction

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“…Since prostaglandins contract the uterus and affect the vasculature, it is assumed that they have a role in the menstrual process. An overproduction of PGF2g by the endometrium is the probable cause of dysmenorrhoea (Lundstr6m et al, 1976), whereas an imbalance of uterine prostaglandin production in favour of prostacyclin (PG12) may be the cause of menorrhagia (Smith et al, 1981). The reasons for these disorders of menstruation are unknown, but may be due to intrinsic factors, such as the higher than normal production of endogenous hormones which affect uterine prostaglandin synthesis (e.g.…”

Section: Introductionmentioning

confidence: 99%

The effect of caffeine on prostaglandin output from the guinea‐pig uterus

Naderali

Poyser

1994

British J Pharmacology

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1 Caffeine increased the outputs of prostaglandin F2,. (PGF2.a), PGE2 and 6-keto-PGFI, from the guinea-pig uterus on days 7 and 15 of the oestrous cycle. The effect on PGE2 output depended on the age of the animals and was absent in younger guinea-pigs (<4 months). Theophylline also stimulated the outputs of PGF2,. and 6-keto-PGFI6, but not the output of PGE2, from the day 7 guinea-pig uterus. 2 The stimulatory effects of caffeine on the outputs of PGFu, PGE2 and 6-keto-PGFI. from the guinea-pig uterus were not prevented by lack of extracellular calcium, ryanodine or ruthenium red (both inhibitors of calcium release via the ryanodine receptor), although the increase in PGFu. output tended to be slower when extracellular calcium was absent. Also, ryanodine flattened and broadened the peak of increased PGFu. release.3 The calmodulin antagonists, W-7 and trifluoperazine, had no inhibitory effect on the caffeinestimulated increases in uterine prostaglandin output. In fact, W-7 (but not trifluoperazine) greatly potentiated the action of caffeine on uterine PGF2, output, but had little or no potentiating effect on the action of caffeine on uterine PGE2 and 6-keto-PGFIc outputs.4 TMB-8, an intracellular calcium antagonist, inhibited the increase in PGF2,, output produced by caffeine without preventing the increases in outputs of PGE2 and 6-keto-PGF1I. 5 These studies suggest that caffeine stimulates uterine PGF2, synthesis and release by a mechanism dependent upon intracellular calcium, but this mechanism is not mediated by activation of any of the three well-characterized ryanodine receptors or by calmodulin. Furthermore, the increases in the synthesis and release of PGE2 and 6-keto-PGFI. in the guinea-pig uterus induced by caffeine appear to involve mechanism(s) different from that which stimulates PGF2. production.

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“…The primary disorder may be related to deficiencies in local production of vasoconstrictors (endothelin-1 and prostaglandin F2a), accelerated lysis of endometrial clot (excessive production of plasminogen activator) [9], or increased local production of prostaglandin E2 and prostacyclin (I2) [10]. AUB-E may also be caused by infection or inflammation of endometrium [1].…”

Section: Methodsmentioning

confidence: 99%

Diagnosis and Management of Formerly Called “Dysfunctional Uterine Bleeding” According to PALM-COEIN FIGO Classification and the New Guidelines

Khrouf

Terras²

2014

J Obstet Gynecol India

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In 2011, the FIGO classification system (PALM-COEIN) was published to standardize terminology, diagnostic and investigations of causes of abnormal uterine bleeding (AUB). According to FIGO new classification, in the absence of structural etiology, the formerly called ''dysfunctional uterine bleeding'' should be avoided and clinicians should state if AUB are caused by coagulation disorders (AUB-C), ovulation disorder (AUB-O), or endometrial primary dysfunction (AUB-E). Since this publication, some societies have released or revised their guidelines for the diagnosis and the management of the formerly called ''dysfunctional uterine bleeding'' according new FIGO classification. In this review, we summarize the most relevant new guidelines for the diagnosis and the management of AUB-C, AUB-O, and AUB-E.Keywords Abnormal uterine bleeding Á Dysovulation Á Menorrhagia Abnormal uterine bleeding (AUB) has negative impact on women's health and well-being inducing anemia, impacting their quality of life by impairing sexuality, and leads to absenteeism and social embarrassment. Non-structural abnormal uterine bleeding, or the formerly called dysfunctional menometrorrhagia, is a frequent cause of AUB.Until recently, there was confusion in clinical management and in the interpretations of clinical trials due to a

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A Role for Prostacyclin (Pgi2) in Excessive Menstrual Bleeding

Cited by 111 publications

References 9 publications

Cyclooxygenase enzymes and prostaglandins in pathology of the endometrium

Cyclooxygenase enzymes and prostaglandins in pathology of the endometrium

The effect of caffeine on prostaglandin output from the guinea‐pig uterus

Diagnosis and Management of Formerly Called “Dysfunctional Uterine Bleeding” According to PALM-COEIN FIGO Classification and the New Guidelines

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